Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial

BACKGROUND: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. DESIGN AND SETTING: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. Patients and INTERVENTIONS: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. OUTCOME MEASURES: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. RESULTS: At 3 months, the percentage of patients who had reduced drug use by > or =50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. CONCLUSIONS: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.     

Concomitant functional dyspepsia and irritable bowel syndrome decrease health-related quality of life in gastroesophageal reflux disease

OBJECTIVE: Previous studies have reported an overlap between gastroesophageal reflux symptoms, functional dyspepsia (FD) and irritable bowel syndrome (IBS). The aim of this study was to investigate the prevalence of FD and IBS in gastroesophageal reflux disease (GERD) and the effect on health-related quality of life (HRQoL). MATERIAL AND METHODS: FD and IBS prevalence and HRQoL were assessed by means of questionnaires in 215 referred and 48 non-referred (non-care-seeking) GERD patients, proven with 24-h pH-metry. HRQoL in 131 matched controls was used for comparison. RESULTS: In this group of GERD patients 25% had FD (Dutch general population 13-14%), 35% had IBS (Dutch general population 0.6-6%) and 5% had both FD and IBS. Only 35% had neither FD nor IBS. Among referred GERD patients, the prevalence of FD and IBS was higher (p=0.002 versus non-referred). Compared with controls, GERD patients without FD/IBS had lower HRQoL scores on only one of the nine SF-36 subscales (p相似文献   

Crohn＇s disease,fatigue, and infliximab： Is there a role for cytokines in the pathogenesis of fatigue？

AIM： To study the effect of infliximab on fatigue in relation to cytokine levels in Crohn＇s disease （CD） patients.
METHODS： Fourteen CD patients were blinded for treatment and received placebo at baseline, and infliximab 2 wk later, with a follow-up of 4 wk. Blood samples were drawn on a regular basis, and questionnaires on fatigue,depression, quality of life, and clinical disease activity were completed at regular intervals.
RESULTS： After placebo infusion, fatigue scores decreased within 3 d （3.5 points ± 1.1, P ≤ 0.01）, but returned to baseline values 14 d after this infusion.The drop of fatigue scores following infliximab infusion sustained until the end of the study （3.8 points ± 1.4, P ≤ 0.05）. Quality of life was increased at the end of the study compared to baseline values （138.6 ± 9.4 vs179.4＋ 6.7; P ≤ 0.005）, whereas depression scores were decreased （20.4 ± 9.4 vs11.3 ± 2.2; P ≤ 0.01）. No correlation between the severity of fatigue and the level of cytokines was observed.
CONCLUSION： The reduction of fatigue after infliximab infusion is subjective to a placebo effect. The effect of infliximab on fatigue, however, persists while the placebo effect disappears after a short period of time. A clear role of cytokines could not be substantiated.     

Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients

AIM： To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome （IBS） patients and healthy subjects using molecular-based techniques.
METHODS： Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization （FISH） and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction.
RESULTS： The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria （4.2 ± 1.3 vs 8.3 ± 1.9, P 〈 0.01） in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower （6 ± 0.6 vs 19 ± 2.5, P 〈 0.001） in the IBS patients in both fecal and duodenal brush samples than in healthy subjects.
CONCLUSION： Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.     

Revisiting the immunomodulators tacrolimus, methotrexate, and mycophenolate mofetil: their mechanisms of action and role in the treatment of IBD

Inflammatory bowel diseases (IBDs) are thought to result from unopposed immune responses to normal gut flora in a genetically susceptible host. A variety of immunomodulating therapies are applied for the treatment of patients with IBDs. The first-line treatment for IBDs consists of 5-aminosalicylate and/or budesonide. However, these first-line therapies are often not suitable for continuous treatment or do not suffice for the treatment of severe IBD. Recently, efforts have been made to generate novel selective drugs that are more effective and have fewer side effects. Despite promising results, most of these novel drugs are still in a developmental stage and unavailable for clinical application. Yet, another class of established immunomodulators exists that is successful in the treatment of inflammatory bowel diseases. While waiting for emerging novel therapies, the use of these more established drugs should be considered. Furthermore, one of the advantages of using established immunomodulators is the well-documented knowledge on the long-term side effects and on the mechanisms of action. In this review, the authors discuss 3 well-known immunomodulators that are being applied with increased frequency for the treatment of IBD: tacrolimus, methotrexate, and mycophenolate mofetil. These agents have been used for many years as treatment modalities for immunosuppression after organ transplantation, for the treatment of cancer, and for immunomodulation in several other immune-mediated diseases. First, this review discusses the potential targets for immunomodulating therapies in IBDs. Second, the immunomodulating mechanisms and effects of the 3 immunomodulators are discussed in relationship to these treatment targets.     

What predicts mucosal inflammation in Crohn's disease patients?

A number of disease-specific instruments have been created over the last 30 years to assess disease activity in Crohn's disease (CD). These disease activity indices are constituted of clinical and laboratory parameters and their role in predicting disease activity and the course of disease has been reviewed various times. Currently, the severity of mucosal inflammation, assessed by endoscopy, is considered the gold standard for disease activity in CD. In the present review the most frequently used endoscopic disease activity indices and the correlation between mucosal inflammation and clinical disease activity indices, quality of life questionnaires, and biochemical markers is critically appraised. We conclude that no clinical disease activity index or single laboratory parameter of inflammation reliably predicts the mucosal inflammatory disease activity. A new, easy-to-use and robust activity index predicting mucosal inflammation is highly needed to assess the response to investigational drugs in trials and the effect of therapeutical interventions in clinical practice.